Objectives: Pertussis vaccines containing a whole-cell pertussis component have effectively controlled pertussis disease in the US. In recent years, there has been considerable effort aimed at development of less reactogenic acellular pertussis vaccines. Licensing of these vaccines has been hindered by the lack of a laboratory correlate of clinical protection and standardized assays for measurement of immune responses. To address this need, the Laboratory has undertaken the following projects: a) To develop new assays with the goal of defining a serologic correlate of clinical protection. b) To work toward the international standardization of ELISA's used to evaluate the antigen and isotype specific responses to B. pertussis. c) to employ these assays to evaluate the serologic response in individuals either vaccinated with pertussis vaccine or infected with B. pertussis and in animal models of infection. FY95 activities: 1. Organized and implemented an international collaborative study to evaluate immunoassays used in acellular pertussis vaccine efficacy and immunogenicity studies. A panel of serum samples was sent to participating laboratories in 12 countries and data was received from 33 laboratories. Data analysis and preparation of a technical report are in progress. 2. Worked with university, foreign, and manufacturer laboratories to transfer the standardized assays so that these laboratories could use the assays to evaluate the serologic response in clinical trials. Performed validation tests on reagents and approximately 1700 ELISA tests to assess inter- laboratory reproducibility. 3. Continued analysis of immunoassay results on a sub-group of individuals from an NIAID study who received licensed whole cell pertussis vaccine as a primary and one of the 13 different acellular vaccines as a fourth dose and began analysis of results. 4. Completed analysis and publication of serological data from the NIAID-sponsored study of 13 acellular vaccines and demonstrated that antibodies to fimbriae are quantitatively the most important agglutinins in individuals with pertussis or immunized with whole-cell or acellular vaccines. 5. Completed analysis and publication of results that demonstrated by ELISA and immunoblotting that both vaccinated and infected individuals develop an antibody response to the B-oligomer of pertussis toxin that correlated well with the response to holotoxin and demonstrated that human antibodies to B-oligomer inhibited the binding of holotoxin to model receptors. 6. Evaluated the kinetics of the antibody response to pertussis toxin in mice and demonstrated a correlation between measured antibody and in vivo protection to toxin challenge. 7. Continued to evaluate the effect of chemical-treatment and aluminum-adsorption of the toxin on the PT-antibody response in mice.
